Mtb (Mycobacterium tuberculosis) is responsible for 2-3 million deaths annually (WHO, 2004). Despite major technical advancements in extracting information from genome sequences, gene function can only be attributed to ˜58% of the ORFs of Mtb emphasizing the importance of developing novel and creative approaches to better understand gene function and thus, virulence. A key challenge in the post-genomic era is to integrate functional strategies to better understand the molecular mechanism of Mtb virulence. It has become increasingly clear that virulence pathways are mediated by multipart networks of molecular connections and that Mtb fails to execute its function unless it interacts with other proteins. It has also been recognized that physical association between a protein of unknown function and a known protein indicates that the former often has a function related to that of the latter. Furthermore, the development of an in vivo technology to study protein-protein association in genetically intractable pathogens, such as Mtb, can significantly impact the understanding of the mechanism of disease.